Background: Earlier studies in animals using erythropoietin have shown benefits on left ventricular (LV) remodeling after acute myocardial infarction. Erythropoietin has also been shown to be safe and feasible in patients with ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI). Objective: To study the effect of erythropoietin on LV remodeling in patients with acute STEMI treated by fibrinolytic therapy. Methods: A pilot, open-label study that enrolled 7 patients with acute inferior wall STEMI treated with fibrinolytic therapy and randomized to either erythropoietin treatment as an adjuvant to fibrinolytic therapy (n = 4) or to fibrinolytic therapy alone (n = 3). A single-dose of erythropoietin 1,000 units per kilogram was immediately given intravenously following fibrinolytic therapy. LV remodeling was assessed by echocardiogram after randomization and at 12 weeks. Results: Patients in the erythropoietin group tended to have a longer time from symptom onset to randomization than those in the control group (187.5 ± 43.1 versus 70.0 ± 26.5 minutes, p = 0.11) but nevertheless tended to have improvement in percentage change of spherical index (-11.3 ± 3.3 versus 8.8 ± 13.7, p = 0.16). Percentage change in end diastolic volume index (EDVI) (17.0 ± 13.4 versus 39.0 ± 81.6, p = 1.00), end systolic volume index (ESVI) (40.5 ± 25.4 versus 25.5 ± 21.0, p = 0.37), ejection fraction (1.6 ± 7.9 versus 8.3 ± 14.5, p = 0.48), relative wall thickness (RWT) (-32.3 ± 14.1 versus 4.4 ± 32.8, p = 0.29), LV mass index (LVMI) (32.3 ± 22.1 versus 18.9 ± 37.7, p = 0.72) and Wall motion score index (WMSI) (0.26 ± 4.16 versus -7.80 ± 4.41, p = 0.27) were similar in both groups. There was no evidence of erythrocytosis, thrombocytosis or any adverse effects of erythropoietin during the study period. Conclusion: Erythropoietin has a tendency to improve LV remodeling after acute STEMI treated by fibrinolytic therapy.